Impact of Daratumumab Refractoriness on Clinical Outcomes Following CAR T-Cell Therapy for Relapsed/Refractory Multiple Myeloma

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.7090-7090
• Main Authors: Rajeeve, Sridevi, Costa, Bruno Almeida, Jurgens, Eric M, Nishimura, Noriko, Farzana, Tasmin, Firestone, Ross S, Miller, Kevin, Lesokhin, Alexander M., Shah, Gunjan L., Korde, Neha, Tan, Carlyn Rose, Chung, David J., Landau, Heather J., Scordo, Michael, Hassoun, Hani, Maclachlan, Kylee H, Shah, Urvi A., Hultcrantz, Malin, Hamadeh, Issam S., Giralt, Sergio, Mailankody, Sham, Usmani, Saad Z., Hashmi, Hamza
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-206511

Introduction: Ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) are two chimeric antigen receptor (CAR) T-cell products targeting B-cell maturation antigen (BCMA) that have recently been approved for the treatment of relapsed/refractory multiple myeloma (RRMM) with 1-2 prior lines of therapy, based on the results of CARTITUDE-4 and KarMMa-3 trials. While daratumumab (dara) refractoriness is predictive of inferior outcomes with subsequent therapies, not all patients enrolled in these pivotal trials were refractory to this anti-CD38 monoclonal antibody. Therefore, we conducted a single-center retrospective cohort study comparing the clinical outcomes of RRMM patients who received BCMA-directed CAR T-cell therapy based on their dara refractoriness status. Methods: Our analysis included all patients with RRMM who received ide-cel, cilta-cel, or orvacabtagene autoleucel (orva-cel) between April 2018 and November 2023. All patients were dara exposed and divided into two groups according to their dara refractoriness status: dara refractory (DR) and dara non-refractory (DN). Refractory disease was defined according to IMWG criteria as disease that did not respond to therapy (failing to achieve a partial response or better) or as progressive disease within 60 days of the last administered dose. Key outcomes of interest included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Survival outcomes were calculated from the date of infusion. Response categories were determined per IMWG consensus definitions. CRS/ICANS were graded based on ASTCT criteria. Results: Of 127 patients included (41% female, age range: 37-86 years) in the analysis, 28 (22%) were considered DN at the time of CAR T-cell infusion. In the DR group (n=99), 41.4% patients received cilta-cel, 31.3% patients received ide-cel, and 27.3% patients received orva-cel. In the DN group (n=28), 50% patients received cilta-cel, 32.1% patients received ide-cel, and 17.9% patients received orva-cel. All patients except one in the DN group were triple class exposed. The analyzed groups (DR vs DN) had comparable rates of patients with ECOG performance status >0 (68.7% vs 60.7%) and high-risk cytogenetic abnormalities (70.7% vs 71.4%), including del(17p)/TP53 mutation, t(4;14), t(14;16), t(14;20), 1q gain/amp and/or del(1p) by FISH analysis.